A large, randomized, controlled 12-week trial of eszopiclone (Lunesta, Sunovion Pharmaceuticals Inc) in children and adolescents with ADHD and insomnia (http://emedicine.medscape.com/article/1187829-overview?src=wgt_edit_news_lsm&lc=int_mb_1001) was no better than placebo in treating the sleep disorder. This study comes on the heels of an earlier trial (http://www.ncbi.nlm.nih.gov/pubmed/19403468) of zolpidem (multiple brands) that showed similar results.
[quote]

and the commentary:

Second Med Fails to Treat ADHD Kids' Sleep Problems

Deborah Brauser
October 02, 2014

The study included 486 participants from 63 US sites who were recruited between April 2009 and July 2011. Of these, 163 were randomly assigned to receive low-dose eszopiclone for 12 weeks (1 mg for children between the ages of 6 and 11 years, 2 mg for adolescents between the ages of 12 and 17 years), 162 received high-dose eszopiclone (2 mg for the children, 3 mg for the adolescents), and 161 received matching placebo.
All participants were instructed to take their assigned medication orally at bedtime.
The study's primary outcome measure was "change in latency to persistent sleep from baseline to week 12, based on polysomnography."
Secondary measures included wake time after sleep onset, which was also assessed via polysomnography, and scores on the Clinical Global Impression Parent/Caregiver and Child scales and the Conners' ADHD rating scale.
A second long-term, open-label study assessed 55 participants who completed the first double-blind study and 249 new adolescent participants who had no history of eszopiclone use.
Wrong Target?
Results from the first study showed no significant differences in reduced latency to persistent sleep between any of the randomized groups. There were also no significant between-group differences in any of the secondary outcomes.
Treatment-related adverse events (AEs) were reported by 61% of the participants who received high-dose eszopiclone, 59.5% of those receiving the low-dose version of the medication, and 46% of those receiving placebo.
The most frequent AEs reported by the participants receiving eszopiclone were headache (13.8% of the high-dose group, 11.7% of the low-dose group, 11.8% of the placebo group), a distorted sense of taste (13.8%, 14.9%, and 1.2%, respectively), and dizziness (8.2%, 3.7%, and 1.9%, respectively). In addition, 5, 4, and 3 patients, respectively, dropped out of the study because of treatment-emergent AEs.
"As with zolpidem, eszopiclone failed to demonstrate efficacy in children and adolescents with ADHD-related insomnia," the investigators write.
They note that the medication was generally well tolerated over the long term.
Results of the second study showed that 70% of the participants experienced at least 1 treatment-related AE. But only 11.2% of the total group discontinued open-label use of eszopiclone because of an AE. Unsettlingly, though, was the finding that 3% of the participants reported hallucinations and that suicidal ideation was noted by 1% to 2%.
Overall, the researchers note that it is unclear whether the reason why these sleep medications are not effective is because of the pediatric population, because the participants had ADHD, or because of something else entirely. "Studies of these agents in children without ADHD and in adults with ADHD may be informative," they write.
They add that the benzodiazepine binding site on the GABA receptor "may be the wrong pharmacologic target for this population."
Dr Sangral noted that insomnia in children with ADHD is not always related to stimulant use. Instead, it could be that insomnia is caused by their hyperactivity or by circadian rhythm changes. "But we just don't know."
Ineffective Medication Class
"I think the most important take-away point for me is that it doesn't seem like this particular class of medication is very effective in this particular patient population," Judith Owens, MD, director of sleep medicine at Children's National Medical Center in Washington, DC, and professor of pediatrics at George Washington School of Medicine and Health Sciences, told Medscape Medical News.
<table class="imgTableRight" width="120" border="0" cellpadding="0" cellspacing="0"><tbody> </tbody><tbody> <tr> <td class="image"> http://img.medscape.com/news/2014/ht_141002_judith_owens2_120x156.jpg

</td> </tr> <tr> <td class="text"> Dr Judith Owens
</td> </tr> </tbody> </table>[quote]
"It doesn't necessarily mean that these drugs don't have some utility in a non-ADHD population. And in fact, that was one of my concerns with the study design: that it was strictly limited to kids with ADHD," she said.
Dr Owens, who was not involved with this research, also noted a concern that more than 50% of the trial participants were taking some type of stimulant medication to treat their ADHD.
"We know that these stimulant medications can affect sleep. So that sort of muddies the water in terms of really having a clean assessment of efficacy and of adverse events."
She added that she understands that the investigators might have worried that taking the children off their daytime ADHD medication during these studies was potentially unethical, especially in the 1-year open-label trial.
"But I think it also raises some issues about the validity of the results," she said.
"Still, I would say that this class of drugs is probably not very effective in the ADHD population, especially as opposed to a number of trials now that have used melatonin and shown that it seems to be quite effective and well tolerated," said Dr Owens.
She added that it was also interesting to see a pharmaceutical company–funded study with negative results published.
"I would applaud the editorial decision of Pediatrics to publish this, and the authors really deserve credit. I just hope that it doesn't discourage further research," she said.
"There are children who need medications for insomnia, although they should always be in combination with behavioral treatment. If these particular drugs don't work, then we need good efficacy and safety data on others."

While it was admirable that the negative study was published- the bigger worry about this article was that the whole article revolved around pharmaceuticals.

Honestly these doctors need to think outside the box-- the pill box.

My comments were:
Sleep management in ADHD is a very difficult problem- and for most of us who have been diagnosed with ADHD (myself included) there is a lifelong fragility in sleep patterns.
Careful history taking will reveal that most of us were colicky infants who did not sleep well- then were toddlers who could never get to sleep and always had nightmares or parasomnias. BEdwetting is also common.

Equally most of us are highly resistant to sleeping medications and require high doses to get any effect.
In this context, encouraging reliance of sleeping medications is not an intelligent approach. It will lead to long term dependency and polypharmacy.

I was diagnosed ADHD in 2008, at age 46. While stimulants have been very helpful for the inattention problems- overall I have found the standard of medical care for ADHD to be beyond bad-- it is abysmal.

My own researches have led me to rely on the following approaches.
1) Sleep hygeine: avoidance of blue light after sunset, turning of screens after about 9pm

2) Mindfulness and relaxation training
3) Sleep hypnosis
4) Brain wave entrainment via binaural beats and cranial electrical stimulation
5) Chiropractic treatment of underlying pain issues
6) Most surprisingly and most effectively- using an electrically earthed bed sheet to reduce electrostatic charge. The effect of the latter has been the most impressive, both in myself, and in the patients who have opted to follow the research links I have given them:
The Biologic Effects of Grounding the Human Body During Sleep as Measured by Cortisol Levels and Subjective Reporting of Sleep, Pain, and Stress
MAURICE GHALY, M.D.,1 and DALE TEPLITZ, M.A.2
-available at:
http://earthinginstitute.net/research/

In terms of medications:
I have some patients get great benefit from melatonin - but not all.
I have yet to have a success with clonidine in adults.
Guacafine is not available in Australia.
Stephen Stahl in his book "Essential Psychopharmacology" recommends a trial of the old fashioned, sedation antihistamines.
There is some sense in that as histamine is an essential neurotransmitter in the arousal networks of the brain.
As a treatment these things sometimes work- but can cause issues with dry mouth and hangover.

However I strongly recommend the non pharmacological approaches outlined above.
My sleep latency often exceeded 2 hours.
Nowadays it is often less than 5 minutes if I am not suffering back pain.

Flory

10-04-14, 12:21 AM

Over here in the UK it is uncommon to be prescribed hypnotics for more than a week at a time with the exception of drugs like circadin which I think they may scribe for a month (I have this on a repeat script though rarely collect it, to combat sleep issues I have)

My personal thoughts are that excessive use of sleeping pills and anti anxiety meds (months and months) such as midazolam, diazepam zopiclone etc Etc just perpetuate the anxiety disorder/sleep disorder further and it sort of becomes a vicious cycle with dependace similar to what people experience when stopping pain meds.

My consultant always says that it doesn't matter what sleeping pill he gives me if I don't follow it up with proper sleep hygiene and try and work with it my insomnia will never go away. It's too easy to rely on something to knock you out and in the long term it's not beneficial.